Project Summary (Overall) For the brain (or any other biological systems), cells are a fundamentally important level of organization between genes/molecules and networks/systems. The mammalian brain is composed of millions to billions of neurons and non-neuronal cells with diverse properties and extremely intricate connections to form highly specific and hierarchically organized circuits and networks. To unravel the principles of information processing in brain circuits, it is essential to have a systematic understanding of its components ? the cell types, and to have tools to monitor and manipulate them in the living brain to probe their roles in the circuits. However, it is still unclear how many cell types there are in the brain and how to even define them. Recent high-throughput technology advancement, especially in the areas of sequencing and imaging, has created an unprecedented opportunity to collect comprehensive information about individual cells in large scales to enable data-driven cell type classification. We will form a Comprehensive Center on Mouse Brain Cell Atlas, and our goal is to create a comprehensive whole-brain atlas of cell types in the mouse encompassing molecular, anatomical and functional annotations of cell types. We will conduct large-scale single-cell transcriptomic analysis across the entire mouse brain, as well as systematic sampling of neuronal morphology and connectivity in a wide range of brain areas. In selected proof-of-principle cases, we will examine the correspondence among the transcriptomic, morphological, connectional and/or functional properties of the same cells, to gain an understanding what defines a cell type. Finally, we will generate a census of the number and location of cells for each type, and new genetic tools targeting selected cell types. We will establish a Data Core to provide data management systems for integrating the diverse data collections and to provide data processing and mapping infrastructure and expertise to transform raw data into quantitative cell characterization features. We will also establish an Administrative Core to address the operational management of the Center, including fiscal management, project management, strategic planning, progress reporting, and support for collaboration and communication. Altogether this project will create a first version of a comprehensive cell type atlas for an entire mammalian brain with enduring values to the community towards the understanding of brain function in healthy and diseased states.